An integrated computational framework to design a multi-epitopes vaccine against Mycobacterium tuberculosis.
An integrated computational framework to design a multi-epitopes vaccine against Mycobacterium tuberculosis.
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DOI：
10.1038/s41598-021-01283-6
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发表时间：
2021-11-09
影响因子：
4.6
通讯作者：
Albutti A
中科院分区：
文献类型：
--
作者：
Albutti A
结核病（TB）是一种高度传染性疾病，主要影响肺部，由细菌病原体结核分枝杆菌引起。与其他疾病相比，结核病的相关死亡率要高得多，抗药性菌株的迅速出现使情况更加令人担忧。卡介苗（BCG）是唯一获得许可的可用于人类的减毒疫苗，但许多国家已停止使用，因为它不能提供保护性免疫。因此，迫切需要努力鉴定不仅提供高免疫保护而且具有广谱适用性的新的和安全的候选疫苗。考虑到这一点，本文中，我进行了广泛的计算疫苗分析，以调查200个完整的测序基因组的M。结核病鉴定核心候选疫苗，其具有安全、抗原性、无毒和非过敏性表位。为了克服文献报道的基于表位的疫苗的局限性，我通过设计多表位疫苗进行了额外的分析，以实现最大的保护性免疫，并通过选择一种由于其有利的理化特性而易于分析的疫苗，使实验后续研究变得容易。基于这些分析，我确定了两种潜在的疫苗蛋白质，它们满足所有疫苗所需的特性。这两种疫苗蛋白是二酰基甘油酰基转移酶和ESAT-6样蛋白。表位：发现来自二酰基甘油酰基转移酶的DSGGYNANS和来自ESAT-6样蛋白的AGVQYSRAD、ADEEQQQAL和VSRADEEQQ覆盖所有必需的参数，因此用于多表位疫苗构建体。所设计的疫苗描绘了对不同免疫受体的高结合亲和力，并显示出稳定的动力学和严格的货车德瓦尔斯和静电结合能。该疫苗还模拟了大量的初级、次级、三级免疫球蛋白产生以及高白细胞介素和干扰素计数。综上所述，所设计的疫苗是理想的实验评估，以破译其在控制耐药M.结核
Tuberculosis (TB) is a highly contagious disease that mostly affects the lungs and is caused by a bacterial pathogen, Mycobacterium tuberculosis. The associated mortality rate of TB is much higher compared to any other disease and the situation is more worrisome by the rapid emergence of drug resistant strains. Bacillus Calmette–Guerin (BCG) is the only licensed attenuated vaccine available for use in humans however, many countries have stopped its use as it fails to confer protective immunity. Therefore, urgent efforts are required to identify new and safe vaccine candidates that are not only provide high immune protection but also have broad spectrum applicability. Considering this, herein, I performed an extensive computational vaccine analysis to investigate 200 complete sequenced genomes of M. tuberculosis to identify core vaccine candidates that harbor safe, antigenic, non-toxic, and non-allergic epitopes. To overcome literature reported limitations of epitope-based vaccines, I carried out additional analysis by designing a multi-epitopes vaccine to achieve maximum protective immunity as well as to make experimental follow up studies easy by selecting a vaccine that can be easily analyzed because of its favorable physiochemical profile. Based on these analyses, I identified two potential vaccine proteins that fulfill all required vaccine properties. These two vaccine proteins are diacylglycerol acyltransferase and ESAT-6-like protein. Epitopes: DSGGYNANS from diacylglycerol acyltransferase and AGVQYSRAD, ADEEQQQAL, and VSRADEEQQ from ESAT-6-like protein were found to cover all necessary parameters and thus used in a multi-epitope vaccine construct. The designed vaccine is depicting a high binding affinity for different immune receptors and shows stable dynamics and rigorous van der Waals and electrostatic binding energies. The vaccine also simulates profound primary, secondary, tertiary immunoglobulin production as well as high interleukins and interferons count. In summary, the designed vaccine is ideal to be evaluated experimentally to decipher its real biological efficacy in controlling drug resistant infections of M. tuberculosis.
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影响因子：
7.8
作者：
Albutti A;Longet S;McEntee CP;Quinn S;Liddicoat A;Rîmniceanu C;Lycke N;Lynch L;Cardell S;Lavelle EC
通讯作者：
Lavelle EC
影响因子：
14.9
作者：
Cheng, J;Randall, AZ;Sweredoski, MJ;Baldi, P
通讯作者：
Baldi, P
DOI：
10.1093/bioinformatics/bts565
发表时间：
2012-12-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Fu L;Niu B;Zhu Z;Wu S;Li W
通讯作者：
Li W
影响因子：
3.2
作者：
Gillard, Paul;Yang, Pan-Chyr;Castro, Marcela
通讯作者：
Castro, Marcela
影响因子：
6.3
作者：
Genheden S;Ryde U
通讯作者：
Ryde U